[BE西来 第2期]——预BE的意义&对BE试验指导成功及失败案例分享

hello,Dr.Arjun would you please give us a brief introduction of azidus and youself. 你好Dr.Arjun,请给您做下自我介绍以及介绍下Azidus公司。

dr. Arjun i think the race difference is the most concerned to Chinese company.dr. Arjun 我认为种族差异是中国公司最关心的问题。

不同人种间BE结果是否有影响？

BE is based on ratios T/R and allied calculations. That is any difference in Race is present for both treatments and this nullified  由于BE是计算受试样品和参比制剂的比率。所以受试品和参比制剂的人种差异都是同时存在的。因此就抵消了。

We want to highlight : all global agencies such as USFDA / EMA / WHO who are the pioneers in BE allow this.另外，我想强调的是：全球机构如USFDA/EMA/WHO 都接受其他人种的BE数据。

That is they accept BE studies performed in India – as even if population has an influence its for both T and R – and for generics this is allowed。他们接受在印度开展的BE研究——即使人种差异有影响，在受试样品和参比制剂的比例中抵消了。

With regard to an example let me explain ;我举个例子

If a PrE BE is positive ; ideally the true BE / pivotal cannot fail .But it can in the following cases ;原则上讲，一个好的预BE结果一定会导致一个好的BE结果，但也会碰到一个好的预BE结果，最终正式BE失败的情况；

1. Wrong sample size – that is in the pivotal BE if the number of subjects are wrong ; even a good product will fail.失败案例-正式BE中受试人数量选错了。

2. Wrong blood collection points : if there is a difference from what was used in PrE 。BE取样点选错：使用了与预BE不同的取样点。

3. Different analytical method : that is a new lab is used and method of analysis is inaccurate than the PrE 。不同的分析方法：在新实验室中使用了相较预BE不准确的分析方法；

To avoid this ; at AZIDUS we provide a design recommendation after the PrE BE for the final BE ; if this is followed for the final BE – there cannot be surprises.

Azidus 采用的方法是，完成预BE后会提供一个建议的BE方案。如果按照这个方案来做正式BE的话。应该不会出现超出预期的结果。

dr. Arjun does us fda consider any race difference？

dr. Arjun ，那USFDA考虑人种差异吗？

Not for BE studies ; only in phase trials . That is for a newly invented drug.对BE而言没有任何人种的差异，只有在做临床的时候才会有这样的考虑，也就是说全新的新药才会考虑人种。

For BE USFDA accepts pivotal BE from India ; all generics are approved that way. AZIDUS has conducted over 110 submissions for USFDA which have been approved – we have been inspected by them 4 times

美国FDA完全接受印度做的BE实验报告。AZIDUS已经向美国FDA递交了110个BE报告，而且已经接受了4次审计。

how to decide the number of subjects in offical BE？

如何确定正式BE受试者数量？

The only time Race May matter is in some specific cases of adverse events ; for example a drug called Cinacalcet – when given to Asians causes vomiting ; but in Europeans the vomiting is less. Still, the BE parameters remain the same in both populations.说到药物对人种的影响。比如西那卡塞，亚洲人吃了比较容易呕吐，欧洲人很少。但是BE数据还是一样的，没有区别。说明BE结果是不受人种差异影响的。

For the number of subjects :

We look at the ISCV value obtained in the PrE BE Study and also the ISCV parameter available in literature.Azidus From this information , a good statistician will be able to calculate number of subjects required for a full BE ; this is commonly done with SAS software. We use professor Chow’s methodology . For all PrE BE studies done at AZIDUS – we provide a sample size estimation for the pivotal as well.

获取预BE的ISCV数据和参考文献中ISCV数据，基于这些信息，一个好的统计人员可以使用SAS软件计算出BE试验所需样本量。我们使用Chow 教授的方法。在AZIDIU做的所有预BE研究，我们均会为客户提供关键的样本量估算。